The invention relates generally to an implantable cardiac stimulation device for the purpose of monitoring the progression of congestive heart failure or the efficacy of delivered heart failure therapies.
Congestive heart failure (CHF) is a debilitating, end-stage disease in which abnormal function of the heart leads to inadequate blood flow to fulfill the needs of the body""s tissues. Typically, the heart loses propulsive power because the cardiac muscle loses capacity to stretch and contract. Often, the ventricles do not adequately fill with blood between heartbeats and the valves regulating blood flow become leaky, allowing regurgitation or back flow of blood. The impairment of arterial circulation deprives vital organs of oxygen and nutrients. Fatigue, weakness, and inability to carry out daily tasks may result. Not all CHF patients suffer debilitating symptoms immediately. Some may live actively for years. Yet, with few exceptions, the disease is relentlessly progressive.
As CHF progresses, it tends to become increasingly difficult to manage. Even the compensatory responses it triggers in the body may themselves eventually complicate the clinical prognosis. For example, when the heart attempts to compensate for reduced cardiac output, it adds muscle causing the ventricles to grow in volume in an attempt to pump more blood with each heartbeat. This places a still higher demand on the heart""s oxygen supply. If the oxygen supply falls short of the growing demand, as it often does, further injury to the heart may result. The additional muscle mass may also stiffen the heart walls to hamper rather than assist in providing cardiac output.
CHF has been classified by the New York Heart Association (NYHA) into four classes of progressively worsening symptoms and exercise capacity. Class I corresponds to no limitation wherein ordinary physical activity does not cause undue fatigue, shortness of breath, or palpitation. Class II corresponds to slight limitation of physical activity wherein such patients are comfortable at rest, but wherein ordinary physical activity results in fatigue, shortness of breath, palpitations, or angina. Class III corresponds to a marked limitation of physical activity wherein, although patients are comfortable at rest, even less than ordinary activity will lead to symptoms. Class IV corresponds to inability to carry on any physical activity without discomfort, wherein symptoms of CHF are present even at rest and where increased discomfort is experienced with any physical activity.
Current standard treatment for heart failure is typically centered around medical treatment using angiotensin converting enzyme (ACE) inhibitors, diuretics, and digitalis. It has also been demonstrated that aerobic exercise may improve exercise tolerance, improve quality of life, and decrease symptoms. Heart transplantation is an option, but only in one out of every two hundred cases. Other cardiac surgery may also be indicated, but only for a small percentage of patients with particular etiologies. Although advances in pharmacological therapy have significantly improved the survival rate and quality of life of patients, patients in NYHA Classes III or IV, who are still refractory to drug therapy, have a poor prognosis and limited exercise tolerance. Cardiac pacing has been proposed as a new primary treatment for patients with drug-refractory CHF.
By tracking the progression or regression of CHF more closely, treatments can be administered more effectively. Commonly, patients adapt their lifestyle and activities to their physical condition. The activity level of the patients with NYHA Class III or IV would be much lower than that of the patients with NYHA Class I or II. The change in lifestyle or activity level, due to the patient""s heart condition, will be reflected by activity and respiration physiological parameters.
Besides various assessments of the cardiac function itself, assessment of activity and respiration are typically performed. This includes maximal exercise testing in which the heart rate and maximum ventilation are measured during peak exertion. However, peak exercise performance has been found to not always correlate well with improvements in a patient""s clinical condition. Therefore, sub-maximal exercise testing can also be performed, such as a six-minute walk test. While improvements in sub-maximal exercise may suggest an improvement in clinical condition, sub-maximal exercise performance can be variable in that it is dependent on how the patient happens to be feeling on the particular day of the test.
To obtain a more general assessment of the patient""s activity on a daily basis, patients are often asked to answer questionnaires regarding numerous aspects of daily life. Such questionnaires are inherently subjective. Nevertheless, collected information is useful to the physician. Since existing CHF treatments are palliative and not curative, a major goal in administering therapies is to improve the quality of daily life which is directly reflected by the level and variety of activities the patient is comfortable performing.
Thus, it would be desirable to have an objective means of chronically and non-invasively monitoring physiological parameters indicative of a patient""s overall well-being on an ongoing, daily basis. This would enhance the physician""s ability to optimize and carefully tailor therapies for stabilizing CHF.
A number of attempts have been made previously to, provide for chronic monitoring of physiological parameters associated with CHF using implantable cardiac devices, such as pacemakers, in conjunction with physiological sensors. Reference is made to U.S. Pat. No. 5,518,001 to Snell; U.S. Pat. No. 5,944,745 to Rueter; U.S. Pat. No. 5,974,340 to Kadhiresan; U.S. Pat. No. 5,935,081 to Kadhiresan; U.S. Pat. No. 6,021,351 to Kadhiresan et al.; and U.S. Pat. No. 5,792,197 to Nappholz. Reference is also made to U.S. Pat. No. 4,901,725 to Nappholz, et al.; and U.S. Pat. No. 5,964,788 to Greenhut, that generally describe rate-responsive pacemakers using impedance measurements of respiration for controlling the pacing rate.
U.S. patent application Ser. No. 09/746,235, entitled xe2x80x9cSystem and Method for Monitoring Progression of Cardiac Disease State Using Physiologic Sensors,xe2x80x9d filed Dec. 21, 2000, describes a technique for monitoring physiological parameters associated with the progression, stabilization, or regression of symptoms of heart disease such as congestive heart failure (CHF). The monitoring is implemented by ongoing surrogate measurement of standard and direct measurements, such as daily activity and respiratory and cardiac rate response, utilizing existing implantable, rate-responsive stimulation devices that incorporate activity, respiration, and/or other sensors. The system includes a sensor that measures activity and/or minute ventilation when triggered by changes in the sensed intrinsic heart rate and/or changes in a sensor-indicated pacing rate. The system processes and displays the measured activity or minute ventilation data to interpolate diagnostic relationships between activity, minute ventilation, heart rate, or sensor-indicated pacing rate, that are representative of the overall well-being of the patient, thus reflective of the severity of CHF symptoms. Activity and minute ventilation data collected upon each heart rate or sensor-indicated pacing rate change are stored in histogram bins assigned to defined heart rate or sensor-indicated pacing rate ranges. After a predetermined period of data collection, the data for each rate range is averaged and statistical or mathematical analysis is performed to determine correlation or regression coefficients that define the relationships between activity, heart rate, sensor-indicated pacing rate, or minute ventilation. A graphical display of the stored averages and the relationship coefficients may be provided for analysis. U.S. patent application Ser. No. 09/746,235 is incorporated herein by reference in its entirety.
Although the techniques of U.S. patent application Ser. No. 09/746,235 help fulfill the need for a method of chronically and objectively monitoring related physiological indicators of the severity of CHF to thereby reflect a worsening or improving condition associated with therapy delivery, room for improvement remains. In particular, it would be desirable to provide a technique for more directly and effectively measuring the severity of CHF based on measurements of heart rate, arterial oxygen saturation, right ventricular O2, stroke volume, tidal volume, respiration rate, etc. and, in particular, for providing a technique for generating a warning signal to the patient or physician if the risk of mortality exceeds a critical threshold. It is to these ends that aspects of the present invention are primarily directed.
In this regard, recent studies have suggested that ventilatory response to exercise (i.e. minute ventilation divided CO2 volume at peak exercise) and chronotropic index (i.e. heart rate reserve as a function of exercise) may be effective predictors of the severity of CHF. See xe2x80x9cVentilatory and Heart Rate Responses to Exercise: Better Predictors of Heart Failure Mortality Then Peak Oxygen Consumptionxe2x80x9d, Robbins et al., Circulation, Dec. 14, 1999. Accordingly, aspects of the invention are also directed to generating a combined CHF metric based both on estimates of the ventilatory response to exercise and chronotropic index. Other aspects are directed to techniques for estimating the ventilatory response to exercise using various measurement proxies, particularly surrogates for a direct measurement of CO2 volume.
In accordance with a first aspect of the invention, a method is provided for determining a risk of mortality to CHF using an implantable medical device having a plurality of sensors and a control unit for processing signals received from the sensors. Based on information received from the sensors, the control unit determines a value representative of a risk of mortality to CHF for the patient, then compares the value with a threshold value and generates a warning signal if the risk of mortality exceeds the threshold value. In this manner, if the severity of CHF increases to the point that it exceeds a critical threshold, the warning signal is generated to thereby advise the patient or physician to take appropriate steps such as initiating more aggressive medical therapy.
The risk of risk of mortality to CHF for the patient may be determined based either on ventilatory response to exercise of the patient or heart rate reserve as a function of exercise for the patient. The control unit then generates a single CHF risk metric based on both ventilatory response and heart rate reserve as a function of exercise. Both the ventilatory response of the patient and the heart rate reserve as a function of exercise for the patient may be determined at sub-maximal exertion levels. Thus, it is not necessary for the patient to exercise at a maximum level to determine the CHF risk metric.
In an exemplary embodiment, ventilatory response is estimated based on heart rate, arterial oxygen saturation, right ventricular O2, stroke volume, tidal volume, and respiration rate detected at sub-maximal exertion levels. Heart rate reserve as a function of exercise is estimated by measuring actual patient heart rates at various sub-maximal levels of exertion, determining heart rate reserve at the various sub-maximal levels of exertion based on the actual heart rates and then predicting the heart rate the patient would achieve if healthy at various levels of exertion. The CHF metric is then calculated by dividing time-averaged ventilatory response values at the various sub-maximal levels of exertion by the slope of heart rate reserve as a function of predicted heart rate.
In accordance with a second aspect of the invention, various methods for estimating ventilatory response are provided. In one method, ventilatory response is estimated by receiving signals representative of heart rate, arterial oxygen saturation, right ventricular O2, stroke volume, tidal volume, respiration rate and then calculating:
VR=(Tidal Volumexc3x97Respiratory Rate)/(1.14xc3x97(Arterial O2xe2x88x92Right ventricular O2)xc3x97(Heart Rate)xc3x97(Stroke Volume)).
In another method, ventilatory response is estimated by multiplying the ventilation amplitude by the ventilation rate (used as a proxy for respiration response) and correlating with the sinus rate. As yet another alternative, since CO2 production is correlated with most activity, activity sensors are used as a surrogate for determining CO2 production. With this latter technique, a minute ventilation sensor value is divided by an activity sensor value (scaled appropriately) and then correlated with sinus rate to yield an estimate of VR.
Thus various techniques are provided for estimating ventilatory response using an implantable medical device and for automatically evaluating risk of mortality due to CHF also using the implantable medical device. Other objects, features and advantages of the invention will be apparent from the detailed description to follow.